ABCA1 p.Leu375=
c.1125G>C · rs748653643 · VCV1799006
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0846%, eas)
Conditions
1
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -4.2 |
| Overall | ||
| CADD | 1.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0846%
East Asian · 38/44,894 alleles
Filtering AF
0.0633%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0559%
Overall
0.0026%
42/1,614,050 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0846% | 1,181 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- ABCA1
- Protein
- p.Leu375=
- Coding
- c.1125G>C
- MANE Select
- NM_005502
- dbSNP
- rs748653643
- Type
- single nucleotide variant
- Location
- chr9:104837497 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.50 · 7 PDB
- Residue 375
- an α-helix; the 'annulus domain 2' region
Similar variants
- ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ABCA1 p.Thr940Met Pathogenic/Likely pathogenic ★★ same condition
- ABCA1 c.3787+5C>A Uncertain significance ★★ same condition
- ABCA1 p.Ala1855Ser Uncertain significance ★★ ⚠ same condition
- ABCA1 p.Ala766Ser Uncertain significance ★★ ⚠ same condition
- ABCA1 p.Arg1283Cys Uncertain significance ★★ ⚠ same condition
- ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ same condition
- ABCA1 p.Arg1417Cys Uncertain significance ★★ ⚠ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca1-p-leu375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown